Browsing by Subject "alcoholic liver disease"

Now showing 1 - 6 of 6
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    The Activation and Function of Autophagy in Alcoholic Liver Disease
    (Bentham Science Publishers, 2017) Khambu, Bilon; Wang, Lin; Zhang, Hao; Yin, Xiao-Ming; Pathology and Laboratory Medicine, School of Medicine
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    Association between Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism and Alcoholic Liver Disease
    (Elsevier, 2018) Chang, Binxia; Hao, Shuli; Zhang, Longyu; Gao, Miaomiao; Sun, Ying; Huang, Ang; Teng, Guangju; Li, Baosen; Crabb, David W.; Kusumanchi, Praveen; Wang, Li; Liangpunsakul, Suthat; Zou, Zhengsheng; Medicine, School of Medicine
    Background Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD); though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods ALDH2 genotype was performed in 535 healthy controls and 281 patients with ALD. Results The prevalence of the common form of the SNP rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, p<0.0001). Among controls, 23.7% had heterozygous (glu/lys) genotype when compared to 4.6% in those with ALD (OR 0.16, 95%CI 0.09–0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%; compared to 14.5% in healthy controls (OR 0.13, 95%CI 0.07–0.24). Conclusions Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.
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    Concomitant Psychiatric and Nonalcohol-Related Substance Use Disorders Among Hospitalized Patients with Alcoholic Liver Disease in the United States
    (Wiley, 2018-02) Jinjuvadia, Raxitkumar; Jinjuvadia, Chetna; Puangsricharoen, Pimpitcha; Chalasani, Naga P.; Crabb, David W.; Liangpunsakul, Suthat; Medicine, School of Medicine
    Background Despite that the epidemiological studies on the comorbidity of alcohol misuse and psychiatric disorders have been studied, less is known about the magnitude of these disorders among patients with alcoholic liver disease (ALD). Our aim was to determine the prevalence of psychiatric and substance use disorders among hospitalized ALD patients in the United States. Methods We utilized a single-level clinical classification software to identify patients with ALD and psychiatric/substance use disorders from the 2011 National Inpatient Sample data. The primary outcome was the prevalence of these disorders among hospitalized patients with ALD (n = 74,972) compared to those with chronic liver diseases not caused by alcohol (n = 350,140) and those without underlying liver diseases (n = 1,447,063). Results The prevalence of adjustment disorder, anxiety disorder, posttraumatic stress disorder, and depression was significantly higher among hospitalized patients with ALD when compared to those with chronic liver diseases not caused by alcohol (all with p-values <0.05). Younger age, female gender, and White race were the independent predictors of psychiatric/substance use disorders among hospitalized patients with ALD. Conclusions Hospitalized patients with ALD have significantly high prevalence of concomitant psychiatric and substance abuse disorders when compared to those with chronic liver diseases not caused by alcohol and those without underlying liver diseases. Screening and appropriate intervention should be implemented as part of routine clinical care for these patients.
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    Introducing the 2019 American Association for the Study of Liver Diseases Guidance on Alcohol‐Associated Liver Disease
    (Wiley, 2020-01) Lucey, Michael Ronan; Im, Gene Y.; Mellinger, Jessica L.; Szabo, Gyongyi; Crabb, David W.; Medicine, School of Medicine
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    MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6–p47phox–oxidative stress pathway in neutrophils
    (BMJ, 2017-04) Li, Man; He, Yong; Zhou, Zhou; Ramirez, Teresa; Gao, Yueqiu; Gao, Yanhang; Ross, Ruth A.; Cao, Haixia; Cai, Yan; Xu, Mingjiang; Feng, Dechun; Zhang, Ping; Liangpunsakul, Suthat; Gao, Bin; Department of Medicine, IU School of Medicine
    Objectives Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. Designs Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled. Mice were fed an ethanol diet for 10 days followed by a single binge of ethanol. Results Compared with healthy controls or alcoholics without recent drinking, alcoholics with recent excessive drinking had higher levels of circulating neutrophils, which correlated with serum levels of alanine transaminase (ALT) and aspartate transaminase (AST). miRNA array analysis revealed that alcoholics had elevated serum miR-223 levels compared with healthy controls. In chronic-plus-binge ethanol feeding mouse model, the levels of miR-223 were increased in both serum and neutrophils. Genetic deletion of the miR-223 gene exacerbated ethanol-induced hepatic injury, neutrophil infiltration, reactive oxygen species (ROS) and upregulated hepatic expression of interleukin (IL)-6 and phagocytic oxidase (phox) p47phox. Mechanistic studies revealed that miR-223 directly inhibited IL-6 expression and subsequently inhibited p47phox expression in neutrophils. Deletion of the p47phox gene ameliorated ethanol-induced liver injury and ROS production by neutrophils. Finally, miR-223 expression was downregulated, while IL-6 and p47phox expression were upregulated in peripheral blood neutrophils from alcoholics compared with healthy controls. Conclusions miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady.
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    Posttraumatic Stress Disorder in Patients with Heavy Alcohol Consumption and Alcoholic Hepatitis
    (Wiley, 2018) Samala, Niharika; Lourens, Spencer G.; Shah, Vijay H.; Kamath, Patrick S.; Sanyal, Arun J.; Crabb, David W.; Tang, Qing; Radaeva, Svetlana; Liangpunsakul, Suthat; Chalasani, Naga; Medicine, School of Medicine
    Background Lifetime prevalence of posttraumatic stress disorder (PTSD) in the general population is reported to be 6.8%. Individuals with alcohol dependence and substance abuse have high prevalence of PTSD. However, the prevalence of PTSD in heavy drinkers with alcoholic hepatitis (AH) is not known.The study's aim was to determine the prevalence of PTSD in heavy drinkers with and without AH. Methods We screened for PTSD using the Primary Care‐PTSD questionnaire among heavy drinkers with (n = 115) and without (n = 64) AH participating in a multicenter observational study in which participants were followed up to 12 months following their enrollment. Results The prevalence of PTSD in heavy drinkers with AH was 34% and was not different from heavy drinking controls without liver disease (34%). In the entire group screened for PTSD, the presence of PTSD was associated with higher alcohol consumption as reported by average drinks per last 30 days and average grams of alcohol consumed per day (p = 0.047 for both tests), but not associated with relapse of heavy drinking or mortality. Similarly, patients with AH and PTSD did not have higher relapse rate or higher mortality compared to patients with AH but no PTSD. Conclusions Compared to previously reported prevalence in general population, heavy drinking individuals with or without AH have significantly higher prevalence of PTSD. However, PTSD was not associated with higher relapse rate or higher mortality in this population.